Guanabenz in VWM

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Amsterdam UMC

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

31 May 2021 → 29 Dec 2025

Decision date (initial)

2024-09-26

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2023-503320-89-00

EudraCT number

2017-001438-25

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To evaluate the safety and tolerability profile of guanabenz in pediatric patients with VWM

Secondary objectives 4

1. To evaluate the PK profile of guanabenz in pediatric patients with VWM
2. To evaluate how quantitativeMRI parameters relevant to brain white matter integrity change over time in pediatric patients with VWM receiving guanabenz.
3. To evaluate how quality of life and disability change over time in pediatric patients with VWM receiving guanabenz as compared to historical controls
4. To evaluate overall survival in pediatric patients with VWM receiving guanabenz as compared to historical controls

Conditions and MedDRA coding

Vanishing White Matter

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Each patient’s parents/legal guardians must sign an informed consent form (ICF) indicating that they understand the purpose of and procedures required for this study, are willing for their child to participate in the study and attend all scheduled assessments (on site or by video consultation as indicated per protocol), and are willing and able to comply with all study-related procedures, including maintaining contact with the site for at least 1 year up to 4 years depending on time of trial entry, and adhere to the prohibitions and restrictions as specified in the protocol.
2. Male or female who has a maximum disease duration of 8 years.
3. Genetically provenVWM with 2 clinically relevant mutations in one of the EIF2B1-5 genes and a brain MRI compatible with the diagnosis.
4. Disease onset before the age of 6 years.
5. Able to stand up and walk at least 10 steps with or without the support of one hand. The “support of one hand” should be light. It does not refer to full support or to physically propelling the child forward
6. Lives within reasonable travel distance from Amsterdam.

Exclusion criteria 8

1. Clinically asymptomatic.
2. Comorbidity with another genetic defect.
3. Presence of an unrelated serious condition (eg, developmental anomaly, cardiac, liver or kidney disease).
4. Participation in another clinical study with therapeutic intervention.
5. Unable or unwilling to come to the study site as required by the protocol.
6. Unable to undergo MRI due to metal-containing implants, such as cochlea implant, neurostimulator or pacemaker.
7. Family situation in which adherence to the study medication or follow-up procedures cannot be guaranteed.
8. Known allergy or hypersensitivity to guanabenz or to any of the other components of the formulation used in this study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. All adverse events and serious adverse events collected from the start of study treatment until the end of the study, applying the most recent version of the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, version 5.0, 27-Nov-2017), as well as applying

Secondary endpoints 4

1. Guanabenz PK parameters in plasma, such as Cmax, AUC, half-life, and predicted trough concentration (Ctrough) at steady state
2. Quantitative brain MRI parameters:
3. Clinical parameters:
4. Overall survival

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 7

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Amsterdam UMC

Sponsor organisation

Amsterdam UMC

Address

P. O. Box 7057

City

Amsterdam

Postcode

1007 MB

Country

Netherlands

Scientific contact point

Organisation

Amsterdam UMC

Contact name

Prof Dr MS van der Knaap

Public contact point

Organisation

Amsterdam UMC

Contact name

Prof Dr MS van der Knaap

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications